1. Field of Invention
The present invention relates to novel aromatic oxazepinones, thiazepinones and diazepinones and sulfur analogs thereof and is particularly concerned with aromatic 1,4-oxazepinones, thiazepinones, diazepinones and thiones of all, which have the aromatic component fused into the oxazepine, thiazepine or diazepine component, each component thereby having two commonly shared carbon atoms and the oxazepine, thiazepine or diazepine ring having an oxo (or thioxo) function on the carbon atom adjacent to one of the shared carbon atoms and a short chain aminoalkyl, alkylaminoalkyl or heterocyclicaminoalkyl radical attached to the carbon atom two positions away from the other shared carbon atom, the compounds having antihistaminic and anti-allergy utility, and a novel process and novel intermediates for the preparation thereof.
2. Information Disclosure Statement
3-Aryl-1,4-benzoxazepin-5(4H)-ones substituted on the oxazepine nitrogen by an aminoalkyl radical have been disclosed by Schenker, K. in Swiss Pat. No. 505.850 (C.A. 75 98600s).
Conversion of flavanones into benzoxazepinones substituted in the 2-position by a phenyl radical has been disclosed by Levai, A. and Bognar, R., Top. Flavanoid Chem. Biochem. Proc. Hung. Bioflavonoid Symp. 4th Ed. 1973 (Pub. 1975) 119-23 (C.A. 85, 79098n). Thione derivatives were obtained by treating with phosphorus pentasulfide.
Certain chemical intermediates, the 1-substituted-3-substituted phenoxypyrrolidines illustrated by
1-methyl-3-(2-carbamoylphenoxy)pyrrolidine, PA0 1-benzyl-3-(2-carbamoylphenoxy)pyrrolidine, and PA0 1-methyl-3-(2-carboxyphenoxy)pyrrolidine, PA0 E is selected from oxygen, sulfur or loweralkyl substituted nitrogen, PA0 B is selected from oxygen or sulfur; PA0 R is selected from the group consisting of hydrogen, PA0 n is 1, 2 or 3; PA0 R.sup.4 and R.sup.5 are selected from hydrogen or loweralkyl (1-5 C); PA0 Z is selected from the group consisting of --NR.sup.1 R.sup.2, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-imidazol-2-yl, 4,5-dihydro-1H-imidazol-2-yl; PA0 E is oxygen, sulfur, or loweralkyl substituted nitrogen, PA0 R is selected from the group consisting of loweralkyl, cycloalkyl or phenyl-loweralkyl, of which phenyl may be optionally substituted by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro or trifluoromethyl; PA0 R.sup.3 is hydrogen or an acid neutralizing ion; PA0 R.sup.4 and R.sup.5 are hydrogen or loweralkyl (1-5 C); and PA0 n is one or two, PA0 to give a compound of the formula ##STR12## or its free base wherein X is chlorine or bromine and A, E, R, R.sup.4, R.sup.5, Y and n are the same as the starting values. Among suitable halogenating agents are PA0 (a) thionyl halides PA0 (b) triphenylphosphine and a carbon tetrahalide PA0 (c) phosphorus pentahalides PA0 (d) phosphorus trihalides, and PA0 (e) triphenylphosphine dihalide. PA0 (a) formaldehyde and formic acid to give a tertiary dimethylamine, PA0 (b) a dihalide or alkenedihalide to give a heterocyclic amine, PA0 (c) a dialdehyde and sodium cyanoborohydride to give a heterocyclic amine, PA0 (d) equal molar amounts of aldehyde or ketone, sodium cyanoborohydride with large excess of above primary amine to give a secondary amine, PA0 (e) equal molar amounts of the primary amine and sodium cyanoborohydride with at least two equivalents of aldehyde or ketone, PA0 (f) in sequence: trifluoroacetyl chloride, alkyl or phenyl-alkyl halide, potassium hydride and potassium hydroxide to give a secondary amine,
in an otherwise novel class are disclosed in U.S. Pat. No. 3,577,415.